This invention relates to novel 1,2-diaminocyclohexane platinum complexes having a salicylate or catecholate ligand.
Cisplatin, an approved drug for the treatment of testicular, ovarian and bladder cancers, is described in U.S. Pat. Nos. 3,892,790 and 3,904,663. Other platinum complexes which have demonstrated anti-tumor activity clinically include 1,1-dicarboxylato(diammine)platinum(II), cis-dichloro-trans-dihydroxy-bis(isopropylamine)platinum-(IV), and 4-carboxyphthalato(1,2-diaminocyclohexane)-platinum (II). These complexes are described in U.S. Pat. Nos. 4,169,846; 4,137,248; and 4,394,319, whose disclosures are incorporated herein by reference.
Each of these prior art complexes consist of platinum bound to two amine ligands on one side of the molecule and either chloride ions or dicarboxylate ions on the other side of the molecule. This arrangement of atoms is consistent with the structure-activity relationships for active platinum complexes first defined by Cleare and Hoeschele (Bioinorganic Chemistry, 1973, 2, p. 187). To date, all reported active platinum complexes have the configuration of two inert amine ligands and two labile halide or carboxylate ligands arranged in a cis configuration. Gondolphi, et al reported the synthesis of triphenylphosphine platinum-catechol complexes which were not appreciably active (Inorganica Chim Acta, 1983, 80, p. 103).